| BackgroundGestational diabetes mellitus(GDM)is one of the most common medical complications of pregnancy.It is acknowledged that GDM increases the risk of pregnancy complications and adverse perinatal outcomes,and influenced maternal and infant health in the future.Previous studies suggested several clinical parameters in early pregnancy were associated with the risk of GDM,but the conclusions were still controversial.ObjectiveThe objectives of this study were to analyze the clinical characteristics of Chinese women with GDM,investigate the clinical risk factors of GDM in the first trimester and build clinical prediction models of GDM according to clinical parameters in the first trimester.Some clinical indices with potential predictive value for GDM reported in the previous studies were also evaluated in this study.MethodsThis was a prospective double-center observational cohort study.All participants underwent clinical laboratory investigation at the first prenatal visit in early pregnancy(6-12 weeks of gestation)and 75-g oral glucose tolerance test(OGTT)during 24-28 weeks of gestation.Binary logistic regression analyses were performed to determine the risk factors of GDM and build clinical prediction models for GDM.Receiver operating characteristic curve analysis was used to evaluate the predictive ability of different prediction models and clinical indices for GDM.Results(1)A total of 1988 pregnant women were enrolled in this cohort study and 1546 pregnant women with completed baseline clinical data underwent 75g OGTT during 24-28 weeks of pregnancy.The prevalence of GDM was 29.49%(456/1546).(2)The fasting blood glucose(FBG),insulin and C-peptide in the first trimester among women with GDM were significantly higher than those in the NGT group.The proportion of caesarean sections and large for gestational age infant in the GDM group were significantly higher than those in the NGT group.(3)Age,prepregnancy body mass index(preBMI),FBG,red blood cell(RBC),alanine aminotransferase/aspartate aminotransferase(ALT/AST),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C)and insulin were independent risk factors of GDM.The clinical prediction models of GDM constructed by clinical parameters presented limited predictive value for GDM.ROC-AUC of the prediction model including age,preBMI,FBG,RBC,ALT/AST,TG,and HDL-C for GDM was 0.709,with the sensitivity of 55.02%and specificity of 76.32%.(4)Several clinical indices,including HOMA-IR,HSI,TG/HDL-C,TyG and TyHGB,could predict the risk of GDM,but the clinical application value of those indices was limited.ConclusionA variety of clinical parameters were independent risk factors of GDM.The prediction models of GDM constructed by multiple clinical parameters and some clinical indices reported in previous studies suggested limited predictive value for GDM.More sensitive and reliable biomarkers need to be explored to achieve the purpose of early prediction and diagnosis of GDM.BackgroundGestational diabetes mellitus(GDM)impairs the health of the mother and offspring,increasing the social and economic burden.The current clinical diagnosis of GDM depends on oral glucose tolerance test during 24-28 weeks of gestation,but the fetal damage caused by GDM in early pregnancy is irreversible at this stage.Therefore,earlier screening and predication of GDM are of great clinical significance.However,there has not been effective biomarker for early prediction of GDM.ObjectiveThe objective of this study was to perform serum and urinary metabolomics analyses to find effective early predictive biomarkers of GDM and to establish the early prediction model for GDM,achieving early recognition and intervention of GDM.MethodsThis study was based on a prospective double-center observational cohort study.Serum samples and urine samples were collected from pregnant women during 6-12 weeks of gestation.Samples in GDM group and normal glucose tolerance(NGT)group were matched according to age,family history of diabetes mellitus and pre-pregnancy body mass index.Non-targeted liquid chromatography tandem-mass spectrum metabolomics analyses were performed in serum and urine samples.Results(1)There were 150 serum samples(GDM=73,NGT=77)and 152 urine samples(GDM=75,NGT=77).(2)A total of 1032 metabolites were identified in serum.There were 97 serum differential metabolites between GDM group and NGT group,of which 62 metabolites levels were higher and 35 metabolites levels were lower in GDM group.Five serum metabolites,including Leukotriene E4,PGP(18:1(11Z)/18:3(9Z,12Z,15Z)),PS(16:1(9Z)/20:4(5Z,8Z,11Z,14Z)),VPGPR Enterostatin and Taurodeoxycholic acid,were expected to be used as early predictive biomarkers of GDM.ROC-AUC of Leukotriene E4 for GDM was the highest,reaching 0.975,with sensitivity of 97.4%and specificity of 90.4%.(3)A total of 1653 metabolites were identified inurine.There were 134 serum differential metabolites between GDM group and NGT group,of which 50 metabolites levels were higher and 84 metabolites levels were lower in GDM group.Five urine metabolites,including Asp Lys Arg Glu Lys,Asp Asp Met Glu,cyclic N-Acetylserotonin glucuronide,Arg Lys Ser His,Phenylalanyl-Glycine,were expected to be used as early prediction biomarkers of GDM.AUC of a panel of five urine metabolites for GDM was 0.973,with sensitivity of 94.8%and specificity of 96.0%.(4)Differential metabolites in serum and urine involved several common and unique metabolic pathways.Further analysis suggested metabolites involved in common metabolic pathways were more closely related to GDM.The three most significant common metabolic pathways were glycerophospholipid metabolism,tryptophan metabolism and folate biosynthesis.ConclusionDisorders of glycerophospholipid metabolism,tryptophan metabolism and folate biosynthesis were important in the development of GDM.Non-targeted metabolomics analyses in serum and urine samples suggested differential metabolites in the first trimester could be potential early predictive biomarkers of GDM.BackgroundThe maternal physiological changes which occur during gestation are complex and affect diverse systems in the body.Elucidating the various changes that occur during pregnancy may assist with understanding maternal health and the factors affecting pregnancy outcomes and only a few of studies performed urinary proteome analyses in gestational diabetes mellitus(GDM).ObjectiveThe objective of this study was to analyze the dynamic changes of urine proteome during longitudinal pregnancy and screen for biomarkers that have predictive value for GDM.MethodsThis was a prospective cohort study enrolled 84 pregnant women.Urine samples were collected from pregnant women during the first,second,and third trimesters(6-8 weeks,22-24 weeks,and 32-34 weeks,respectively).This study performed serial urinary proteome analyses using a data-independent acquisition(DIA)approach to compare physiological and pathophysiological changes during gestation in normal pregnancy and women with GDM.The differential proteins in the GDM group were then verified using a parallel reaction monitoring(PRM)approach.Results(1)Among the 84 pregnant women,15 women were diagnosed with GDM,19 women were diagnosed as having had an SA before 12 weeks of gestation,and 50 were normal pregnant women.(2)249 urinary proteins were identified as serially changed proteins in normal pregnancies.The functional and pathway analyses of the three trimesters demonstrated that the urinary proteome differed in terms of protein composition and function during gestation,suggesting that it may reflect the physiological changes of pregnancy.(3)In the GDM group,216 urinary proteins were identified as serially changed proteins.A total of 48,90,and 82 urinary proteins were found to be differentially expressed between GDM group and control group during the first,second,and third trimesters,respectively.The 21 altered urinary proteins during the first trimester were validated using targeted LC-PRM-MS.Marked differences were observed in three urinary proteins,NOV,PRDX5,and HGFL,that also play central parts in the network of insulin effect.A panel of NOV,PRDX5,and HGFL could achieve an AUC value of over 0.9.(4)A total of 86 urinary proteins were found to be differentially expressed between SA group and control group.The 42 altered urinary proteins were validated using targeted LC-PRM-MS.Four proteins(GDF-15,GNAQ,GBB1,and GNAI3)involved in the upstream estrogen metabolism pathway had higher AUC values,ranging from 0.75 to 0.81,than the other proteins.ConclusionUrinary proteomes could reflect physiological and pathophysiological changes during gestation.A panel of NOV,PRDX5,and HGFL could predict GDM and become potential prediction biomarkers of GDM.Urinary proteomic analyses in SA might provide valuable clues for the pathogenesis. |
